Axillary Radiotherapy Research Articles

Axillary Surgery Following Neoadjuvant Chemotherapy – Multidisciplinary Guidance From the Association of Breast Surgery, Faculty of Clinical Oncology of the Royal College of Radiologists, UK Breast Cancer Group, National Coordinating Committee for Breast Pathology and British Society of Breast Radiology

AimsThese multidisciplinary guidelines aim to provide clinically helpful, evidence-based recommendations on the surgical management of the axilla in patients who have received neo-adjuvant chemotherapy for early breast cancer. Materials & methodsFollowing a review of published evidence, a writing group representing all disciplines quorate within a breast cancer multidisciplinary meeting prepared the guidelines. Key recommendationsIn patients presenting with clinically node negative axillae, sentinel node biopsy (SNB) may be performed prior to or on completion of neo-adjuvant chemotherapy (NACT). In patients presenting with clinically node positive axillae, SNB may be safely considered following completion of NACT. Four nodes should be removed with dual mapping. If evidence of complete pathological response of previous metastases is seen, axillary radiotherapy may be offered. If residual cancer (isolated tumour cells, micro- or macrometastes) is seen within the SNB, offer axillary node dissection.

Which target volume should be considered when irradiating the regional nodes in breast cancer? Results of a network-meta-analysis

Purpose/objective(s)Radiation treatment to the regional nodes results in an improvement in survival in breast cancer according to a meta-analysis of randomized trials. However, different volumes were targeted in these studies: breast or chestwall only (WBI/CWI), inclusion of the medial supraclavicular region and axillary apex (MS + WBI/CWI) or additional inclusion of the internal mammary chain (IM + MS + WBI/CWI). The benefit of treating the medial supraclavicular region and axillary apex compared to tangential breast or chestwall irradiation only remains unclear.Materials/methodsA literature search was conducted identifying trials for adjuvant radiation volumes in nodal irradiation after breast surgery and axillary treatment. Events and effect sizes were extracted from the publications for the endpoints of overall survival (OS), breast cancer-specific survival (BCSS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional control (LRC). A network meta-analysis was performed using MetaXL V5.3 with the inverse variance heterogeneity model.ResultsWe found two randomized studies (n = 5836) comparing comprehensive nodal irradiation to sole breast treatment as well as one randomized (n = 1407) and one prospective cohort study (n = 3377) analysing the additional treatment of the internal mammary chain against sole local and supraclavicular and axillary apex radiation. Compared to WBI/CWI alone the treatment of IM + MS + WBI/CWI (HR = 0.88; CI:0.78-0.99; p = 0.036) results in improved OS unlike MS + WBI/CWI (HR = 0.99; CI:0.86-1.14; p = 0,89). These results are confirmed in BCSS: IM + MS + WBI/CWI (HR = 0.82; CI:0.72-0.92; p = 0.002) and MS + WBI/CWI (HR = 0.96; CI:0.79-1.18; p = 0.69). PFS is significantly improved with the treatment of MS + WBI/CWI (OR = 0.83; CI:0.71-0.97; p = 0.019). Both nodal treatment volumes improve LRC (MS + WBI/CWI OR = 0.74; CI:0.62-0.87; p = 0.004 and IM + MS + WBI/CWI OR = 0.60; CI:0.43-0.86; p < 0,001). Yet only the internal mammary nodes provide a benefit in DMFS (MS + WBI/CWI HR = 0.97; CI:0.81-1.16; p = 0.74 and IM + MS + WBI/CWI HR = 0.84; CI:0.75-0.94; p = 0.002).ConclusionExpanding the radiation field to the axillary apex and supraclavicular nodes after axillary node dissection reduced loco-regional recurrences without improvement in overall and cancer-specific survival. A prolongation in survival due to regional nodal irradiation is achieved when the internal mammary chain is included. This derives from a reduction in distant metastasis.

Role of Axillary Radiotherapy in Patients of Locally Advanced Carcinoma Breast with Inadequate or unknown Lymph Node Dissection Status - An Institutional Audit

Role of Axillary Radiotherapy in Patients of Locally Advanced Carcinoma Breast with Inadequate or unknown Lymph Node Dissection Status - An Institutional Audit

Development and Validation of a Nomogram to Predict Lymphedema After Axillary Surgery and Radiation Therapy in Women With Breast Cancer From the NCIC CTG MA.20 Randomized Trial

Regional nodal irradiation for women with breast cancer is known to be an important risk factor for the development of upper extremity lymphedema, but tools to accurately predict lymphedema risks for individual patients are lacking. This study sought to develop and validate a nomogram to predict lymphedema risk after axillary surgery and radiation therapy in women with breast cancer. Data from 1832 women accrued on the MA.20 trial between March 2000 and February 2007 were used to create a prognostic model with National Cancer Institute Common Toxicity Criteria Version 2.0 grade 2 or higher lymphedema as the primary endpoint. Multivariable logistic regression estimated model performance. External validation was performed on data from a single large academic cancer center (N = 785). In the MA.20 trial cohort, 3 risk factors were predictive of lymphedema risk: body mass index (adjusted odds ratio, 1.05 per unit body mass index; 95% confidence interval [CI], 1.03-1.08, P < .001), extent of axillary surgery (adjusted odds radio for 8-11 lymph nodes removed, 3.28 [95% CI, 1.53-7.89] P = .004; 12-15 lymph nodes, 4.04 [95% CI, 1.76-10.26] P = .002; ≥16 nodes, 5.08 [95% CI, 2.26-12.70] P < .001), and extent of nodal irradiation (adjusted odds radio for limited, 1.66 [95% CI, 1.08-2.56] P = .02; for extensive, 2.31 [95% CI, 1.28-4.10] P = .004). A nomogram was created from these data that predicted lymphedema risk with reasonable accuracy confirmed by both internal (concordance index, 0.69; 95% CI, 0.64-0.74) and external validation (concordance index, 0.71; 95% CI, 0.66-0.76). The nomogram created from the MA.20 randomized trial data using clinical information may be useful for lymphedema screening and risk stratification for therapeutic intervention trials.

Pneumonitis resulting from radiation and immune checkpoint blockade illustrates characteristic clinical, radiologic and circulating biomarker features

BackgroundPneumonitis is a potential consequence of both lung-directed radiation and immune checkpoint blockade (ICB), particularly treatment with PD-1/PD-L1 inhibitors. Significant morbidity and mortality can result, and severe pneumonitis attributed to ICB precludes continued therapy. Thus, discriminating between radiation- and ICB- related pneumonitis is of importance for the increasing number of patients receiving both treatments. Furthermore, data are limited regarding the interplay between radiation- and ICB-induced lung injury, and which biomarkers might be associated with toxicity.Case presentationWe report longitudinal clinical and radiologic data, and circulating biomarkers in a melanoma patient treated with axillary radiation followed by ICB who developed consolidation and ground glass opacities (GGO) within the radiation field suggestive of radiation-pneumonitis followed by consolidation outside of the radiation field suggestive of ICB-related pneumonitis. Of note, symptomatic radiation-pneumonitis developed despite a low radiation dose to the lung (V20 < 8%), and ICB-related pneumonitis was limited to the ipsilateral lung, suggesting additive effect of radiation and ICB in the development of lung injury. Circulating biomarker analyses demonstrated increases in CXCR2, IL1ra and IL2ra that coincided with the development of symptomatic pneumonitis.ConclusionsThese data highlight the imaging findings associated with radiation and ICB-related lung toxicity, and anecdotally describe a clinical course with circulating biomarker correlates. This information can help guide clinical evaluation and future research investigations into the toxicity of combined radiation immunotherapy approaches.

Identification and Management of Lymphedema in Patients With Breast Cancer.

Breast cancer-related lymphedema (BCRL) is a potentially debilitating and often irreversible complication of breast cancer treatment. Risk of BCRL is proportional to the extent of axillary surgery and radiation. Other risk factors include obesity and infections. Given the 5-year survival rate of 90% and its potential impact on the quality of life of survivors of breast cancer, BCRL has become a significant financial burden on the health care system. Minimizing axillary surgery and radiation has been proven to reduce the risk of BCRL. Comprehensive multidisciplinary assessment at the time of initial diagnosis; early referral to physical therapy after surgery; and patient education regarding weight loss, skin, and nail care are cornerstones of the management of early-stage lymphedema. End-stage lymphedema may benefit from referral to a plastic surgeon specializing in lymphedema surgery. In this review, we attempt to review the incidence, risk factors, staging, prevention, and management of this complication of breast cancer treatment. We also describe our multidisciplinary approach for the prevention of this complication at the time of initial diagnosis.

Efficacy of complex decongestive therapy on breast cancer-related lymphedema: A cross-sectional study

Aim: Lymphedema is a protein-rich interstitial fluid accumulation which occurs as a result disruption of lymphatic circulation. Breast cancer is a major reason of secondary cancer lymphedema. Breast cancer related upper extremity lymphedema result from the obstruction or disruption of the lymphatic system due to axillary lymph node dissection and/or radiation therapy of axillary region. A variety of conservative therapies have been aimed to decrease the limb swelling and its associated problems have been developed. Conservative treatments are complex decongestive therapy (CDT). The aim of our study was to investigate efficacy of CDT on the occurrence of breast cancer related lymphedema.Methods: Between 2009 and 2018, 47 consecutive patients with histologically proven breast cancer were first treated with breast surgery, axillary lymph node dissection and radiotherapy and/or chemotherapy. These were analyzed collectively with retrospective data of our medical records who had 15-30 set of CDT and who had complete assessments before and after the treatment. CDT consists of the following components; skin care, manual lymphatic drainage, bandaging and exercises. Patients were treated with active therapy schedule (manual massage for lymphatic drainage and exercise therapy, 45-60 min per day) by the same trained physiotherapist. Volumetric quantification by circumference measurement of affected and healthy extremities was used for diagnosis and follow-up of lymphedema in all patients.Results: The data of the 47 patients complying with the criteria specified in this retrospective study were evaluated. When the volumetric changes in the affected extremity were examined before and after lymphedema treatment, it was determined that the amount of lymphedema decreased after CDT (P=0.001). 31 (66%) patients received radiotherapy after mastectomy. When the patients were compared in terms of volumetric changes in extremities before and after CDT according to getting postoperative radiotherapy, it was determined that the changes in the patients who did not get radiotherapy were significantly higher than those getting radiotherapy (P=0.01).Conclusion: Our study results show that CDT can be used for the management of breast cancer related lymphedema of limb. A thorough cost-effective analysis of protocol for CDT should be performed in a future study. In addition, as the factors underlying treatment delay were not included in this study, we believe future studies examining this area may be beneficial.

P004. Intraoperative assessment of sentinel nodes in mastectomy patients

Introduction: Intraoperative sentinel node assessment was routinely offered to patients undergoing curative breast surgery with negative preoperative nodal status. Our previous audit showed 34% patients undergoing mastectomy had positive OSNA results. Axillary radiotherapy is now increasingly being offered to node positive patients with one or two positive sentinel nodes. The aim of this audit was to assess the rate of positive sentinel nodes in patients undergoing mastectomy.

P005. Axillary radiotherapy is non inferior to completion axillary clearance in patients with positive sentinel lymph node biopsy - a single-centre observational cohort study

P005. Axillary radiotherapy is non inferior to completion axillary clearance in patients with positive sentinel lymph node biopsy - a single-centre observational cohort study

Lymphedema Incidence After Axillary Lymph Node Dissection: Quantifying the Impact of Radiation and the Lymphatic Microsurgical Preventive Healing Approach.

Axillary surgery and radiotherapy are important aspects of breast cancer treatment associated with development of lymphedema. Studies demonstrate that Lymphatic Microsurgical Preventive Healing Approach (LYMPHA) may greatly reduce the incidence of lymphedema in high-risk groups. The objective of this study is to summarize the evidence relating lymphedema incidence to axillary lymph node dissection (ALND), regional lymph node radiation (RLNR) therapy, and LYMPHA. We performed a literature search to identify studies involving breast cancer patients undergoing ALND with or without RLNR. Our primary outcome was the development of lymphedema. We analyzed the effect of LYMPHA on lymphedema incidence. We chose the DerSimonian and Laird random-effects meta-analytic model owing to the clinical, methodological, and statistical heterogeneity of studies. Our search strategy yielded 1476 articles. After screening, 19 studies were included. Data were extracted from 3035 patients, 711 of whom had lymphedema. The lymphedema rate was significantly higher when RLNR was administered with ALND compared with ALND alone (P < 0.001). The pooled cumulative incidence of lymphedema was 14.1% in patients undergoing ALND versus 2.1% in those undergoing LYMPHA and ALND (P = 0.029). The pooled cumulative incidence of lymphedema was 33.4% in those undergoing ALND and RLNR versus 10.3% in those undergoing ALND, RLNR, and LYMPHA (P = 0.004). Axillary lymph node dissection and RLNR are important interventions to obtain regional control for many patients but were found to constitute an increased risk of development of lymphedema. Our findings support that LYMPHA, a preventive surgical technique, may reduce the risk of breast cancer-related lymphedema in high-risk patients.

OA38 - Regional Recurrence Rates with or Without Complete Axillary Dissection for Breast Cancer Patients with Node-Positive Disease on Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy

Abstract Purpose Current standard of care for patients with breast cancer with a positive node on sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy is axillary dissection with irradiation of the regional nodes, but it is unknown whether axillary lymph node dissection (ALND) can be safely omitted if complete axillary radiation is delivered instead. Methods and Materials We identified 161 patients found to have a positive sentinel lymph node on SLNB after neoadjuvant chemotherapy for breast cancer between December 2006 and October 2017, who were treated with or without completion ALND. Local, regional, and distant recurrence and overall survival were analyzed using the Kaplan-Meier method. Patient, disease, and treatment factors potentially predictive of each outcome were entered into Cox regression analysis. Results Median follow-up was 28.8 months (range, 2.5-137.0). The 3-year regional control rate did not differ according to extent of axillary surgery (92.6% for SLNB alone vs 96.4% for SLNB with ALND, P = .616). Regional recurrence occurred as part of first recurrence in 9 patients (5.6%). Five patients failed in axillary levels 1 or 2, 6 failed in axillary level 3 or supraclavicular nodes, and 2 failed in internal mammary nodes, with some patients failing in multiple regional nodal areas. Extent of axillary dissection (SLNB only vs SLNB plus ALND) did not predict for disease control or survival. Patients who underwent ALND were significantly more likely to have lymphedema (25.0% vs 9.4%, P = .021). Conclusions Careful selection of patients with a positive sentinel node on SLNB after neoadjuvant chemotherapy for omission of completion ALND in favor of irradiation of the undissected axilla does not compromise local, regional, or distant control or overall survival and results in lower rates of lymphedema.

Prevalence and Intensity of Persistent Post-Surgical Pain following Breast Cancer Surgery: A Systematic Review and Meta-Analysis of Observational Studies

POSTER ABSTRACTIntroduction/Aim: Persistent post-surgical pain (PPSP) is a common complication after breast cancer surgery; but reported prevalence rates range from 10% to 69%. We conducted a systematic review to address this uncertainty.Methods: We searched MEDLINE, EMBASE, CINAHL and PsycINFO from inceptionto October 2018, to identify observational studies that reported the prevalence and intensity of PPSP after breast cancer surgery. We performed random effects meta-analysis with Freeman-Tukey transformation for overall, moderate and severe PPSP prevalence, and pooled pain intensity after converting all pain scales to the 10cm VAS.Results: We included 188 observational studies with 300,025 patients. The overall prevalence of any PPSP was 34.5% (95%CI 30.1% to 39.2%). The pooled prevalence of moderate and severe pain was 14.9% (95%CI 11.5% to 18.7%) and 4% (95%CI 2.7% to 5.5%) respectively. The average pain intensity on a 10cm VAS was 2.7 (95%CI 2.2 to 3.1).We are completing analyses to inform PPSP prevalence and intensity at <1 year, 1–2 years, 2–3 years and >3 years, and prevalence of neuropathic pain. We will also perform subgroup analyses for risk of bias, any pain vs. specific pain, axillary lymph nodes dissection and radiotherapy, and meta-regression for the association between PPSP and length of follow-up and proportion of loss to follow-up.Discussion/Conclusions: PPSP after breast surgery is common and affects approximately 1 in 3 women undergoing this procedure. Of those who develop persistent pain, 43% will report at least moderate pain and 12% will experience severe pain although the average pain is mild.

&lt;p&gt;Axillary management still needed for patients with sentinel node micrometastases&lt;/p&gt;

More attention has been paid to the axillary management over the past 50 years, and clinical practice has been changed as results of the random controlled trials. The American College of Surgeons Oncology Group Z0011 and International Breast Cancer Study Group (IBCSG) 23-01 trials provided high-level evidence to support the omission of axillary lymph nodes dissection (ALND) in sentinel lymph node (SLN)-positive patients receiving breast-conserving surgery (BCS) and adjuvant systemic treatment. In patients treated with BCS, whole breast irradiation (WBI) with tangential fields could lead to substantial axillary irradiation and control the residual tumor burden in axilla, whereas (intraoperative) partial breast irradiation has no therapeutic effect on these residual axillary metastases. In the observation group of the IBCSG 23-01 trial, 425 patients received BCS and 80 (18.8%) of them just underwent intra-operative radiotherapy. While the 10-year axillary recurrence rate was acceptable low (1.7%, 8/467) in the no ALND group, it was 4.5% (6/134) in patients without axillary management, which was significantly higher than that of 0.6% (2/333) in patients with axillary management (P=0.0024). Should we accept an axillary recurrence rate as high as 4.5% in patients with only SLNs micrometastases? What is the best way to control the residual tumor burden in the axilla and decrease the recurrence rate if there is no ALND? The evidence showed that both WBI after BCS (Z0011, AATRM [Agència d’Avaluació de Tecnologia i Recerca Mèdiques]) and axillary regional nodal irradiation after mastectomy/BCS OTOASOR (Optimal Treatment Of the Axilla - Surgery Or Radiotherapy), AMAROS (After Mapping of the Axilla: Radiotherapy Or Surgery) could control the regional residual tumor burden when the SLN is positive and an ALND is omitted. In the modern era, systemic therapy could further decrease the risk of local/regional recurrences. After the subanalysis of the POSNOC (POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy), SERC (Sentinelle Envahiet Randomisation du Curage), and Dutch BOOG (BOrstkanker Onderzoek Groep) trials, a prediction model might be established to identify those patients who could beneft from no axillary management as a guide to clinical practice. At present, axillary management should still be required for patients with SLN micrometastases.

Abstract GS4-01: Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: 10 year follow up results of the EORTC AMAROS trial (EORTC 10981/22023)

Abstract Background: Sentinel node biopsy (SNB) is standard in assessing axillary lymph node status in patients with clinically node-negative breast cancer. The 5-year analysis of AMAROS trial showed that if locoregional treatment is advised after a tumor-positive axillary SNB, axillary radiotherapy (ART) is a reasonable alternative for an axillary lymph node dissection (ALND) with less side effects, though follow up was relatively short. Here we present the 10-year follow up data. Methods: From February 2001 to April 2010, patients with primary breast cancer stage cT1-2N0M0 were enrolled in the EORTC phase III non-inferiority AMAROS trial by 34 European sites. Patients were randomized between ALND and ART in case of a tumor-positive SNB. The primary endpoint, axillary recurrence rate (AxR) is now assessed at 10 years in the ITT population using Fine and Gray cumulative incidence method with deaths as competing risks, as well as secondary endpoints: overall survival (OS), distant metastasis free survival (DMFS), second primaries (including cancers other than breast cancers and contralateral DCIS) and locoregional recurrences (LRR). Little extra information beyond 5 years was available concerning Quality of Life and morbidity. Data collection is still ongoing and will be presented later. Results:Of the 4806 patients entered, 1425 patients had a tumor-positive SNB: 744 in the ALND-arm and 681 in the ART-arm, 60% with a macrometastasis. Both treatment-arms achieved a median 10-year follow-up and were comparable regarding age, tumor size, grade, tumor type and adjuvant systemic treatment. In the group who had ALND, the 5-year AxR was 0.41% (95%CI: 0.00;0.88) (4/744) and the 10-year AxR was 0.93% (95%CI:0.18;1.68) (7/744). In the group who had ART, the 5-year AxR was 1.04% (95%CI: 0.27;1.81) (7/681) and the 10-year AxR was 1.82% (95%CI: 0.74;2.94) (11/681) (HR 1.71, 95%CI: 0.67;4.39, p = 0.37). Sensitivity analysis, considering deaths and distant recurrences as competing risks, revealed consistent results. There were no significant differences between treatment arms regarding OS (ALND: 84.6% (95%CI: 81.5;87.1), ART: 81.4% (95%CI: 77.9;84.4), HR 1.17, 95%CI: 0.89;1.52, p= 0.26) and DMFS (ALND: 81.7% (95%CI: 78.5;84.4), ART: 78.2% (95%CI: 74.6;81.3), HR 1.18, 95%CI: 0.92;1.50, p=0.19). Cumulative incidence estimates of 10-year LRR are 3.59% (95%CI: 2.12;5.06) (ALND) versus 4.07% (95%CI: 2.49;5.65) (ART) (p= 0.69). More second primaries were observed after ART: 75/681 (21 contralateral breast) as compared to ALND: 57/744 (11 contralateral breast) (p = 0.035). All results are consistent in the per protocol analysis of patients with a tumor-positive SNB. Conclusion: Axillary recurrence after 10 years in patients with a tumor-positive SNB who were treated with ART is extremely rare and not significantly different from patients who were treated with ALND. OS, DMFS and locoregional control are also comparable. Second primaries including contralateral breast cancers are more frequently encountered after ART, but the difference is still low in absolute numbers. Thus, ART is a safe treatment for breast cancer patients with a tumor-positive SNB. Citation Format: Rutgers EJ, Donker M, Poncet C, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Blanken C, Orzalesi L, Klinkenbijl JH, van der Mijle HC, Veltkamp SC, van 't Riet M, Albregts M, Marinelli A, Rijna H, Tobon Morales R, Snoj M, Bundred N, Chauvet MP, Merkus JW, Petignat P, Schinagl DA, Coens C, Peric A, Bogaerts J, van Tienhoven G. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: 10 year follow up results of the EORTC AMAROS trial (EORTC 10981/22023) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-01.

Abstract PD8-05: POSNOC - Positive sentinel node: Adjuvant therapy alone versus adjuvant therapy plus clearance or axillary radiotherapy

Abstract Background: Role of additional axillary treatment (AxT) (axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) in women with ≤2 macrometastases and undergoing systemic therapy remains unclear. Z11 included both micro and macrometastases (around 40% micrometastases) and showed that ALND may be omitted in women with ≤2 positive nodes undergoing breast conserving surgery (BCS) and receiving whole breast RT. Paradoxically, NCIC MA20, demonstrated improved DFS following the addition of regional RT. 51.8% (949/1832) had 1 or 2 positive nodes. 98.9% (1812/1832) had T1/T2 tumours. A post-Z11 survey shows that most US radiation oncologists treat the undissected axilla in women with macrometastases with ART rather than omitting AxT. Therefore, a confirmatory study is needed to clarify the role of additional AxT in women with ≤2 macrometastases undergoing BCS and other subgroups that were not included in Z11 e.g. mastectomy, microscopic extranodal invasion and sentinel node biopsy (SNB) before neoadjuvant chemotherapy. Methods: Primary objective is to assess whether for women with ≤2 macrometastases at SNB, systemic therapy alone is non-inferior to systemic therapy plus AxT in terms of axillary recurrence at 5 years. Secondary objectives are arm morbidity assessed by LBCQ and QuickDASH questionnaires; QoL assessed by FACT-B+4 questionnaire; anxiety assessed by STAI; loco-regional recurrence; distant metastasis; time to axillary recurrence; axillary recurrence-free survival; DFS; OS; contralateral breast cancer; non-breast malignancy; and economic evaluation. Eligibility criteria include: ≥18 y, uni or multifocal invasive cancer, T1/T2, 1 or 2 macrometastases, with or without extranodal invasion. Target sample size is 1900 with a projected drop-out and non-compliance with treatment allocation rate of 10%. Primary analysis will be per protocol. The following pre-specified subgroup analyses shall be performed: number of macrometastases (1, 2), age (&amp;lt;50, ≥50), breast surgery (mastectomy, BCS), ER (positive, negative), tumour grade (1 or 2, 3), SN assessment technique (OSNA, non-OSNA), extranodal invasion (present, absent). POSNOC opened to recruitment in July 2014. To date 1100 women have been recruited at 82 sites in the UK and 18 sites in Australia and New Zealand. Clinicaltrials.gov NCT02401685. Citation Format: Goyal A, Mann B, Thompson AM. POSNOC - Positive sentinel node: Adjuvant therapy alone versus adjuvant therapy plus clearance or axillary radiotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD8-05.

Abstract P1-12-18: Mechanical properties of the shoulder and pectoralis major in women undergoing breast conserving therapy with axillary dissection and regional nodal radiotherapy versus sentinel node biopsy and radiotherapy to the breast alone

Abstract Background: Breast conserving surgery (BCS) and radiotherapy (RT) reduce the risk of breast cancer recurrence, but can cause various functional deficits in breast cancer survivors. Side effects to the shoulder can include pain, stiffness, and restricted mobility, which are difficult to objectively assess in the clinic. Methods: The mechanical integrity of the shoulder and the pectoralis major (PM) was assessed in patients at least 1 year post-treatment with BCS and RT. Nine patients with node-negative breast cancer were treated with 2 RT fields to the breast alone after BCS and sentinel node biopsy (Group 1). Nine patients with node-positive breast cancer were treated with ≥3 RT fields to the breast and draining lymphatics after BCS and axillary lymph node dissection (ALND) (Group 2). Nodal RT was delivered to the supraclavicular and infraclavicular (level III axillary) nodes in 9/9 patients, the internal mammary nodes in 6/9 patients, and the full axilla (levels I, II, and III) in 1/9 patient. Nine age-matched healthy controls (mean age 54) with no history of breast cancer or shoulder injury were also examined. The mechanical integrity of the shoulder was objectively quantified using robot-assisted biomechanical measures of shoulder stiffness. The shear elastic modulus, or 'stiffness', of the clavicular and sternocostal fiber regions of PM was assessed using ultrasound shear wave elastography. Participants were examined while they were relaxed or actively contracting force with their shoulder muscles. Linear mixed effect models with Bonferroni-corrected multiple comparisons were used to determine if shoulder stiffness or PM shear elastic modulus differed between the two breast cancer groups and controls. Results: Patients in Groups 1 (mean age 54) and 2 (mean age 57) were an average (SD) 754(111) and 988(163) days since initiating RT (p=0.003). Shoulder stiffness did not differ between the 2 groups and healthy controls (F2,27=0.76, p=0.48), There was a significant group difference in PM shear elastic modulus (F2,27=8.33, p=0.0015), with Group 2 patients exhibiting an average greater stiffness of 14-21% in the sternocostal and 12-28% in the clavicular regions of the PM versus Group 1 patients (p&amp;lt;0.001) and healthy controls (p =0.021). There was no difference between patients treated with Group 1 and controls (p=0.29). Conclusions: Although power is limited due to small sample size, this study provides the first evidence that the mechanical integrity of the shoulder remains intact in patients who receive ALND combined with a supraclavicular field (generally without full axillary radiotherapy). The observation of altered PM function without subsequent changes to shoulder stiffness in patients treated with ALND and ≥3 RT fields suggests these patients likely develop new neuromuscular strategies to stabilize the shoulder joint to compensate for the PM. Future work is needed to appreciate whether certain muscle strategies are associated with poorer quality of life in breast cancer survivors, and to prospectively monitor the impact of breast cancer treatments on PM mechanical properties. Citation Format: Lipps DB, Leonardis JM, Lehmann S, Dess RT, McGinnis G, Strauss JB, Hayman JA, Pierce LJ, Jagsi R. Mechanical properties of the shoulder and pectoralis major in women undergoing breast conserving therapy with axillary dissection and regional nodal radiotherapy versus sentinel node biopsy and radiotherapy to the breast alone [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-18.

Abstract P1-12-13: Initial report of a prospective, pilot study of patient-reported upper extremity dysfunction in women undergoing radiation for breast cancer

Abstract Objectives: Upper extremity dysfunction (UED) is a known side effect of breast cancer treatment. It is unclear, however, to what degree radiation contributes to this morbidity. We aimed to characterize the level of UED using patient-reported outcomes (PROs) prior to, during, and after treatment with radiation for breast cancer. Our secondary aims were to evaluate the association of UED with pain scores. Methods: This is a single-institution, prospective, longitudinal cohort study of patients treated with radiation for breast cancer. The validated patient-reported outcome measure, Quick Disabilities of the Arm, Shoulder and Hand (QD) was used to capture UED prior to radiation, at the end of radiation, and 1 month following the completion of radiation. Pain scores were also collected at these intervals using the numeric pain reporting scale (NPRS) from 0 (no pain) to 10 (worst pain). Results: Forty-four patients were enrolled on this study and 43 (97.7%) had completed radiation at the time of analysis. Thirteen patients (29.5%) were treated with mastectomy, axillary lymph node dissection and regional nodal irradiation in the supine position. The other 31 (70.5%) patients underwent lumpectomy and sentinel lymph node biopsy. Of these patients, 26 (83.9%) were treated in the prone position and 30 (96.8%) received whole breast irradiation. Median time from surgery to radiation was 69 days (range 35 – 212 days), 76 days for mastectomy and 68 days for lumpectomy. Median time from start to end of radiation was 38 days for mastectomy and 28 days for lumpectomy. Pre-treatment median QD score prior to radiation was 12.5 (11.4 for lumpectomy, 15.9 for mastectomy), 9.1 at the end of radiation (9.1 for lumpectomy, 18.2 for mastectomy), and 2.4 at 1 month after radiation (2.3 for lumpectomy, 2.5 for mastectomy). Median NPRS scores at pre-treatment, post-treatment and 1 month follow-up were 1, 1, and 1 for lumpectomy and 0, 1, 0 for mastectomy patients, respectively. Conclusion: In this initial pilot study with 1 month of follow up, patient-reported UED as demonstrated by QD scores were higher pre-radiation and decreased by one month after. This likely reflects recuperation after surgical procedure. Median average pain scores were low at all time points. Further evaluation of UED over time to characterize the long-term effect of radiation and correlation with quality of life and other clinical factors is planned. Citation Format: Healy E, Pan X, Beyer S, Washington I, Bazan J, White J. Initial report of a prospective, pilot study of patient-reported upper extremity dysfunction in women undergoing radiation for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-13.

Abstract ES11-2: Current status of diagnosis, monitoring, and non-surgical management of lymphedema

Abstract Lymphedema (LE) is a common but underreported complication of breast cancer treatment since most studies lack baseline and follow-up measurements or follow-up that is long enough to adequately record true incidence. Contemporary prospective randomized trials continue to document the occurrence of lymphedema after any axillary treatment and note that combination therapy with axillary surgery and radiation nearly doubles LE risk. Over the last 5 years clinicians have witnessed a paradigm shift in the diagnostic practices of LE with concerted efforts focusing on early detection as opposed to reactionary interventions. Controversy however has existed over how to define and diagnose LE and as such the literature surrounding diagnosis is heterogeneous with respect to incidence and recommendations. Existing guidelines emphasize the need for routine monitoring for LE and the critical importance of baseline, bilateral, and longitudinal limb assessments but do not embrace one measurement technique. A growing body of prospective observational data is systematically challenging the value of precautionary behaviors. Further, prospective randomized data demonstrates exercise does not promote the development of LE. Complex decongestive therapy remains the cornerstone of non-surgical LE treatment. With the NCI predicting over 4 million breast cancer survivors in the US by 2024, lymphedema is potentially a significant public health burden. Citation Format: McLaughlin S. Current status of diagnosis, monitoring, and non-surgical management of lymphedema [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES11-2.

Abstract OT2-02-01: A confirmation study of omitting axillary dissection in patients with breast cancer and positive sentinel nodes

Abstract Background The omission of axillary dissection for positive sentinel-node breast cancer is considered the standard treatment for patients who undergo breast conserving surgery and radiation therapy, according to the results of ACOSOG-Z0011 and AMAROS trials. On the other hand, some surgeons still think that the surgical stress of axillary dissection is minimal, and dissection is permitted. Furthermore, Z0011 contains several problems, such as insufficient number of entry cases and lack of radiation field unity. Thus, we planned a prospective trial to confirm the safety of omitting axillary dissection in patients with breast cancer and positive sentinel nodes. Trial design This is a single arm, confirmation study of three medical centers. Prior to surgery, informed consent is obtained, and patients are registered primarily. After surgery, patients with 1 to 2 positive sentinel nodes, for whom axillary dissection was omitted, are finally included in this trial at final registration. Eligibility criteria Patients with histologically-diagnosed breast cancer, Tis–2, N0 based on a core needle biopsy, will be included in this trial. Eligible patients must be between 20 and 80 years of age, with a performance status of 0–2 and adequate organ function. They must not have undergone any prior operation, radiation therapy, chemotherapy, endocrine therapy, or immunotherapy. Specific aims The primary endpoint is 5-year (y) axillary recurrence rate. Secondary endpoints are 5-y overall survival, 5-y recurrence-free survival, 5-y local recurrence-free survival, the rate of upper-limb lymphedema, quality of life, and comparison of axillary recurrence rates between patients with two or more dissected nodes and those with only one positive node. Statistical methods The expected rate of axillary recurrence is 2.0%, and non-inferiority is defined as an axillary recurrence lesser than or equal to 5% in the axillary radiotherapy group. The sample size was calculated with a study power of 80% and type I error of 10% (two-sided). The required number of patients is estimated to be 189. Present and target accrual Patient accrual from the three medical centers was initiated in July 2016. We plan to enroll a total of 189 patients at final registration in this trial. Citation Format: Jibiki N, Hirano A, Ochi T, Sakamoto A, Horiuchi K, Noguchi E, Omi Y, Ogura K, Inoue H, Kamio T, Naritaka Y, Fujibayashi M, Hiroshima K, Nagashima Y, Sakai S, Karasawa K, Okamoto T. A confirmation study of omitting axillary dissection in patients with breast cancer and positive sentinel nodes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-02-01.

Evaluating the Effect of Axillary Lymph Node Involvement and Dissection in the Development of Post-Mastectomy Lymphedema

Background: Lymphedema of the upper extremity is a serious consequence of breast cancer surgery. Postmastectomy lymphedema of the upper limb is usually related to many risk factors, like axillary surgery, radiotherapy, venous obstruction, obesity, and infection. In the current study, the objective was to identify the relationship between the extent of lymph node involvement and axillary dissection on the development of lymphedema. Patients and methods: One hundred and seventy patients managed by modified radical mastectomy with axillary dissection for mammary-invasive adenocarcinoma between January 2009 and December 2016 in Al-Fayhaa Teaching Hospital. The patients were divided into three groups according to the number of lymph nodes involvd, by pathology. The patients had been followed up for at least two years and assessed by standard lymphedema assessment, then categorized into three groups, according to the severity of lymphedema. Results: After the analysis of patient parameters, the highest age group was 36–45 years. More than 60% of the patients had 4–9 lymph nodes involved. Forty-one patients from the 170 developed lymphedema postoperatively. Forty patients had seroma and twenty-one patients had wound infection postoperatively. Conclusion: Post-mastectomy lymphedema is a sequelae of disease process related to the extent of lymph-node involvement and resection rather than operative fault. Key words: breast cancer, mastectomy, lymphedema.